Production of esters of substituted allyl alcohols



hired tates greases PRUDU CTE-GN @F ESTERS 6F SUHESTHTUTED ALLYLALQUHQLS No Drawing. Application July 27, 1953, Serial No. 3766M 9@Eairns. (Ql. 260- 191) This invention relates generally to processesfor making organic chemical compounds, more particularly certain organiccarboxylic acid esters of unsaturated aliphatic and unsaturated aromaticalcohols, and novel chemical compounds obtainable by these processes.These chemical compounds, because of their desirable odors and flavors,are useful in the manufacture of perfumes and certain of the compoundsmay be useful also in insect control and food flavoring.

It is Well known that esters of aryl-substituted allyl alcohols,especially the esters of cinnamyl alcohol, are possessed of pleasantodors and other properties that make them outstandingly importantsubstances for use in the compounding of perfumes, aromatic essences andfood flavoring compositions. However, according to presentday methods ofmanufacture, the cost of producing these esters is high, resulting inthe products being costly, thus limiting their use in commercialpreparations. These manufacturing methods have the disadvantages ofrequiring very expensive starting materials, of involving chemi calreactions that are extremely diificult to control, and of beingsubstantially inoperative for the synthesis of aliphatic unsaturatedalcohol esters, which are desirable and useful products.

These prior art methods are illustrated by the process now used for themanufacture of cinnamyl acetate. The starting material used isbenzaldehyde which is reacted with acetaldehyde in the presence ofcaustic soda to effect an aldol condensation with formation of cinnamicaldehyde as the chief reaction product. The yield in this operation isnot high, due in part to competing side reactions and this fact, inaddition to the cost of the benzaldehyde required as starting material,makes cinnamic aldehyde an expensive substance.

When the cinnamic aldehyde intermediate has been obtained in the mannerdescribed, it is reduced to cinnamyl alcohol by treatment with aluminumisopropoxide or a similar reducing agent that can effect reduction ofthe aldehyde carbonyl group to yield the desired carbinol withoutattacking the double bond of the allyl chain. This reaction usingaluminum isopropoxide involves initial forination of an additionproduct:

which subsequently breaks down to yield the desired alcohol. Thecomparative inefiiciency of this method and the relativelyunsatisfactory yields of cinnarnic alcohol obtained serve further toincrease the cost of the final products. As the final step in the priorart process, the cinnamic alcohol is esterified, by conventionalmethods, to yield the desired esters.

An object of the present invention is to provide methods for producingcertain carboxylic acid esters of unsaturated aliphatic and unsaturatedaromatic alcohols, particularly cinnamyl alcohol esters, which utilizeinexpensive and commonly available starting materials, whereby theseesters can be produced efiiciently and at materially reduced costs,

Another object of the invention is to provide methods for making theseesters without use of a cinnamyl alcohol as an intermediate.

A further object of the invention is to provide processes for makingcinnamyl alcohol esters that are free of the disadvantages,above-mentioned, that are characteristic of the methods presentlyemployed for making the esters.

Other objects, advantages and features of the processes of thisinvention will be obvious to those skilled in the chemical arts from thefollowing description of the invention.

In accordance with this invention, substituted allyl alcohol esters oforganic carboxylic acids are obtained by pyrolysis of certain organiccarboxylic acid esters of a selected 3-acyloxymethoxy-propanol,preferably in the presence of an acid catalyst and at a subatmosphericpressure. The 3-acyloxymethoxy-propyl esters used as starting materialsmay be readily obtained by ring fission of substituted 1,3-dioxanesobtainable by reacting selected aliphatic or aromatic aldehydes witholefins in the presence of an acid catalyst, or the esters may beobtained by other routes of organic synthesis as will be apparent tothose skilled in the chemical arts.

According to the presently preferred embodiment of this invention, the3-acyloxymethoxy-propyl esters are prepared by reacting an alkene oraralkene, selected as hereinafter specified, with a selected aliphaticor aromatic aldehyde in the presence of an acid catalyst to yield asubstituted 1,3-dioxane intermediate product, which then is treated witha selected organic carboxylic acid anhydride to effect fission of thedioxane ring and formation of an intermediate carboxylic acid ester of a3-acyloxymethoxy-propanol.

Illustrative of the alkenes that may be used in production of1,3-dioxanes are:

HQO.OH=OH:

propene isobutene H3O.C=CH.OH3

trimethylethyleue (HaC)aC.OH=C(CHs)2 di-isobutene (HaC)3C.CH2.C=CH2HzC=CH.(CH2)5C/lls octene-l Illustrative of the aralkenes that may beused in production of 1,3-dioxanes are:

CBHLCI'IZCEQ styrene 0CH3.CaH .CI-I==CH2 o-tolylethyleneI)CH3.0EH-,.OH=OH2 p-tolylethylene p--HaC.CoH4.C=CH2wmethyl-p-methyIstyrene CBH5-O=CH2 C lHs m-methylstyrene Although eachof the foregoing alkenes and aralkenes is functionally operative in theproduction of intermediate materials for use in the practice of thisinvention and,

when so utilized, yields final products useful in the perfumery, theintermediate products obtained from the aralkenes, particularly styrene,are especially desirable.

The selected alkene or aralkene is initially reacted,rin the presence ofan acid catalyst, with an aldehyde, preferably formaldehyde, to yield,as an intermediate product, a substituted 1,3-dioxane, whichsubsequently is subjected to esterification and pyrolysis to produce thedesired unsaturated alcohol esters. Among the aliphatic aldehydes thatmay be used instead of the preferred formaldehyde in these operationsare the saturated alkanals comprising at most 7 carbon atoms, of whichacetaldehyde, propionaldehyde, butyraldehyde and heptaldehyde arepreferred. Benzaldehyde is an aromatic aldehyde that may be used in theprocess of this invention.

When the alkene or aralkene above specified is reacted with an aldehydeselected from the mentioned group, the 1,3-dioxane product obtained is acompound of the formula:

2 Ri.( J.CHRs.OHR

O.CHR4.0

wherein:

R1 is a lower alkyl group comprising at most 6 carbon atoms or anaromatic radical chosen from the group consisting of phenyl and tolyl;

R2 and R3 are hydrogen or methyl, not necessarily the same; and

PA is hydrogen, a lower alkyl group comprising most 6 carbon atoms, orphenyl.

The intermediate 1,3-dioxane compound obtained as above described istreated with a selected organic carboxylic acid anhydride, in thepresence of an acid catalyst such as sulfuric acid, to effect scissionof the dioxane ring according to reactions that may be representedgenerally as follows:

wherein R and R6, not necessarily the same, are chosen from the groupconsisting of lower alkyl groups comprising at most 3 carbon atoms andphenyl radicals.

For convenience, this cleavage of the dioxane ring by treatment with aselected anhydride of an organic carboxylic acid anhydride is hereinreferred to as acylolysis.

The preferred reagents for effecting acylolysis are the anhydrides ofthe lower alkanoic acids comprising, in the acid radical, at most 4carbon atoms, such as acetic anhydride, which is especiallysatisfactory, propionic anhydride, butyricanhydride and the like.However, if desired, other carboxylic acid anhydrides may be used, suchas benzoic acid anhydride, benzoic-acetic anhydride and the like.

it is preferable. although not essential, that the acylolysis reactionmixture, throughout the period when the reaction takes place, bemaintained at a temperature merely slightly warmer than roomtemperature, say at a temperature within the range of about 30 C. toabout 40 C., or higher, depending upon the structure and molecularWeight of the compounds being used. As the reaction is exothermic, thistemperature control is effected by agitating and cooling of the mixture.

When the reagents and the reaction products have reached a state ofstable equilibrium, the reaction mixture is treated with an alkalinereagent to eliminate the acid catalyst present. It is preferred,although not essential, that the alkaline reagent for this purpose be analkali metal salt of that organic carboxylic acid of which the anhydridewas used in the acylolysis reaction, for example, sodium, acetate whenacetic anhydride was used. Following the treatment of the mixture withthe alkaline reagent, the separated alkali metal sulfate is removed, forinstance by filtering the mixture, and the acylolysis cleavage products,which remain in the filtrate, are further processed as now will bedescribed.

For convenience, herein, these intermediate products obtained by theacylolysis of the dioxane intermediates will be designated3-acyloxymethoxy-propyl esters with the understanding that this termsignifies the variously substituted compounds of this basic formula asabove set forth.

These last-mentioned intermediates, in accordance with this invention,are now subjected to pyrolysis whereby the 'y-position s-ubstituentgroup is removed with a hydrogen atom from the fi-position, withformation of a carbon-carbon double bond in the ,8- positions of thepropanol chain (i. e., formation of a substituted allyl alcoholcarboxylic acid ester). This pyrolytic reaction may be representedgenerally as follows:

wherein R1, R2, R3, R4, R5 and Re have the significance aforesaid.

This pyrolysis of these substituted 3-acyloxymethoxypropanol carboxylicacid esters to correspondingly substituted allyl alcohol esters can beeffected by heat, merely, at temperatures within the range of about C.to about 300 C. at a sufiiciently reduced pressure, say of the order ofabout 0.5 to at most about 50 millimeters of mercury, that the volatilepyrolysis products are rapidly distilled from the zone where thepyrolysis occurs. Although this temperature range for the pyrolysis stepdefines the operative conditions, below which no satisfactory yields ofthe desired products are obtained and above which undesirable otherreactions and charring of the materials occur, it will be understoodthat the pyrolysis temperature is functionally related to the pressureemployed and hence may be varied in relationship thereto as will beunderstood by those versed in the chemical arts. Moreover, with thecompounds of higher molecular weight, operations obviously should beconducted at somewhat higher temperatures and lower pressures, than aresuitable for lower molecular weight compounds. In general, however, withcompounds of average molecular weight, say when R1 is phenyl, R2, R3 andR4 are hydrogen, and R5 and Rs are methyl, it is preferred that thepyrolysis be performed at temperatures within the range of 180 C. to 220C. at 20 to 50 millimeters pressure, as theseconditions, experienceindicates, give optimum yields of the desired products.

Although, as above mentioned, the pyrolysis of the substituted3aacyloxymethoxy-propanol carboxylic acid esters to correspondinglysubstituted allyl alcohol esters can be effected by heat, merely, attemperatures within the ranges specified, it has been found that thedesired reaction proceeds much more efllciently in the presence of anacid catalyst. This catalyst is a relatively non-volatile acidicsubstance, such as a mineral acid, for instance, orthophosphoric acid orsulfuric acid, but preferably is an acid-reacting alkali-metal salt ofsuch an acid, say sodium or potassium bisulfate; or it can be an organicsulfonic acid, either aliphatic or aromatic, of which benzenesulfonicacid, p-toluenesulfonic acid, m-xylenesulfonic acid and hexanesulfonicacid are representative operative examples. The term relativelynon-volatile acidic substance, as hereemployed, signifies a substancethat is not significantly volatilized from the reaction mixture underthe specified reaction conditions.

The desired substituted allyl alcohol ester products are recovered fromthe pyrolysis distillate by removing the other reaction productspresent, the aldehyde and carboxylic acid, by usual methods, forinstance by water washing when low molecular weight aldehydes are used.The esters are substantially water insoluble.

From the foregoing, it will be apparent that the proc esses of thisinvention may be represented, in general terms, as follows, wherein thevariants of the formulae (R1, R2, R3, R4, R and R6) have thesignificance above set forth:

+ R4OHO 30G 02H It will be understood that the processes of thisinvention also may be utilized in the production of the aliphatic oraromatic alcohols that are represented by the formula:

C=(|3.0HR4.0H R2 R3 which may be obtained readily from the esters,prepared as aforesaid, merely by hydrolysis according to known methodsgenerally applicable to carboxylic acid esters.

To facilitate a better understanding of the principles of thisinvention, certain examples follow wherein the preparation of specificcompounds by the processes of the invention will be described. It willbe understood that these examples are provided for purposes ofillustration merely and are not to be construed as constituting anylimitations upon the scope of the invention defined by the claims.

EXAMPLE 1 Synthesis of cinnamyl acetate O6H5.CH=CHz 2HOHOCGH5.CH.CH2.CH2

( 2304) O.OH2. 0

formaldehyde in an aqueous sulfuric acid reaction medium. The reactionmay be accelerated by heating the mixture, say about 90 C., if desired,and the reaction product, 4-phenyl-l,3-dioxane, is recovered from themixture by conventional methods. About 410 grams (ca. 2.5 moles) of thisreaction product is subjected to acylolysis by treatment with 275 grams(2.7 moles) of acetic anhydride and about 3 grams of concentratedsulfuric acid. Preferably, the sulfuric acid and the acetic anhydrideare mixed prior to addition and the mixture is added to the dioxaneportionwise over a period of to minutes while agitating the mixture andapplying cooling to maintain the temperature of the mixture within therange of about C. to about C. The reaction product here formed is3-phenyl-2-oxa-1,5-pentanediol diacetate. After the initial exothermicreaction following addition of the acid mixture has subsided, theacylolysis reaction mixture is permitted to stand at room temperaturefor a period of approximately 12 hours, then the sulfuric acid presentis rendered ineifeotive by addition of about 20 grams of anhydroussodium acetate, which causes formation and separation, from the mixture,of sodium sulfate. The separated salt may be removed by filtration andthe filtrate, or the gross acylolysis product, is introduced,portionwise over a period of about 1 hour, into a vacuum stillpotcontaining approximately 10 grams of fused potassium bisulfate. Thestillpot temperature is maintained at about 200 C. to 220 C. and thevacuum at about 19 to 22. millimeters of mercury throughout the additionperiod. By means of a suitable fractionating column fitted to thestillpot, a fraction boiling at 146 C. to 149 C. (at a pressure of 18millimeters of mercury) is continuously collected and it is found to becinnamyl acetate (saponification equivalent of the dried, neutralizedmaterial: found, 1763; calculated, 176.1). About 292 grams of the esteris obtained, representing approximately 66.3% of the calculated yield.

EXAMPLE 2 The operations described in Example 1 are repeated except thatthe potassium bisulfate there employed is replaced With an equal weightof p-toluenesulfonic acid.

In this manner, the cinnamyl acetate product (saponification equivalent:found, 173.8; calculated, 176.1) is obtained in an improved yield: about308 grams (70% of calculated).

EXAMPLE 3 The operations described in Example 1 are repeated except thatafter the intermediate reaction mixture is treated with anhydrous sodiumacetate and the treated mixture filtered, it is thereafter subjected topyrolysis as follows: the acylolysis filtrate is introduced into thestillpot containing the fused potassium bisulfate, not portionwise, but,instead, in the full quantity, and the mixture is heated at about 200 C.at a pressure of approximately millimeters of mercury. The distillatefraction boiling at about 172 C. to 177 C. (mainly, at 175 C. to 177 C.)at a pressure of approximately 43 millimeters of mercury substantiallyconsists of cinnamyl acetate (saponification equivalent: found, 176.9;calculated, 176.1). The yield of the desired ester product is about 239grams (about 54.4% of calculated).

EXAMPLE 4 Synthesis of 3,5,5-trimethyl-2-hexerzyl acetate(H8C)IC.OH2.Cl=CH2+2HCHO 15; (HaC)aC-CHz.G.CH2.CH2

(HaCLCOhO AKHSOt dioxane, is obtained as a colorless supernatant oil,which is separated from the aqueous sulfuric acid layer, washed withwater and aqueous soda solution, dried and distilled. The fractionboiling at C. to 225 C. at atmospheric pressure is collected and thisoil is then reacted with a mixture of acetic anhydride and sulfuric acidin substantially the same manner as is described as the acylolysis stepin Example 1, and then the reaction mixture is treated with anhydroussodium acetate to render the sulfuric acid present ineffective. Afterremoving the separated sodium sulfate, the acylolysis product, 3,5,5-trimethyl-3-acetoxymethoxy-hexyl acetate is subjected to pyrolysis insubstantially the same manner as is described in Example 1, using fusedpotassium bisulfate, and the pyrolysis product,3,5,5-trimethyl-2-hexenyl acetate, a hitherto unknown chemical compoundis collected as the fraction boiling at 220 to 225 C. at atmosphericpressure. It is a colorless liquid having a floral or mildly fruityodor. It was conclusively identified by hydrolyzing it to the alcohol,oxidizing the alcohol to the aldehyde, treating the aldehyde with a weakbase to efiect a de-aldol reaction yielding acetaldehyde and the knownmethyl neopentyl ketone.

It will be obvious to those skilled in the chemical arts from theforegoing, that, in like manner, other 3,5,5- trimethyl-Z-hexenyl estersof the lower alkanoic acids, e. g., propionic and butyric acid, may beprepared by replacing the acetic anhydride employed in the acylolysisstep with a different anhydride, e. g., propionic anhydride or butyricanhydride.

EXAMPLE Synthesis of cinnamyl acetate by reduced pressure pyrolysis of3-phenyl-2-oxa-1,S-pentanediol diacetate without use of catalyst3-phenyl-2-oxa-1,5-pentanediol diacetate, which may be prepared asdescribed in Example 1, is placed in a vacuum stillpot, the pressure isadjusted at about 50 millimeters of mercury and heat is applied to thestillpot. Rapid distillation quickly ensues as the head temperaturereaches about 64 C.; at about 90 0., formaldehyde polymer begins to coatthe condenser and receiver; and heating is continued until the pottemperature reaches about 138 C. (about 40 to 45 minutes). The collecteddistillate is diluted with water, the organic layer, after washing withwater is taken up in benzene. The pot liquid is further distilled at 170C. to 179 C., at a pressure of about 51 millimeters of mercury and thisdistillate, dissolved in benzene, is mixed with the benzene solution ofthe first fraction. The combined benzene solutions are washedsuccessively with dilute aqueous ammonia solution, water, dilute aceticacid, and with water again, then the organic fraction is distilled at apressure of 43 to 44 millimeters of mercury. The fraction boiling at 172C. to 177 C. is collected and is found to be cinnamyl acetate (yield,54.4% of calculated; saponification equivalent, calculated, 176.1,found, 176.9). When treated with aqueous sodium hydroxide solution, thisester product is hydrolyzed, yielding cinnamyl alcohol.

EXAMPLE 6 Synthesis of cinnamyl propionate O .CHz.O (113C. CH2. C O)2OCBH5.CH.CH2-CHZO2C.OHLCHB O.CH2.02C.CH:.CH3

AKHSO4 C511 .CH=CH.CHg.OzC.CHg.CHa

night at room temperature. The solution containing the reaction product,3-phenyl-2-oxa-1,5-pentanediol dipropionate, is treated with 0.7 gramanhydrous sodium acetate, filtered and the filtrate is pyrolyzed, usingfused potassium bisulfate as a catalyst, at a pressure of about 22millimeters of mercury in a stillpot heated in an oil bath at 230 C. to245 C. The collected distillate is neutralized with dilute sodiumbicarbonate solution, extracted with benzene and the benzene extract iswashed successively with dilute sulfuric acid and with water, then it isdried and the benzene is distilled off. By fractional distillation ofthe residue at a pressure of 1 millimeter of mercury and collection ofthe fraction that boils in the range 117 C. to 119 C. cinnamylpropionate is obtained (yield, equivalent to 46.1% of the calculatedyield; saponification equivalent, calculated, 190.1, found, 190.6).

EXAMPLE 7 Synthesis of cinnamyl butyrate CaHs.CH.CH2.0Hn

O .CHz.O

(HsC.CH 0112.0 O)2O i H2504 CsH5.CH.CH2.CHz.O2C.CH .CHz.CH3

O.CH2.O2C.OH2.CH2.CH3

IA KHS04 CaH6.CH=CH.CI-I2.0aC.CH2. CH2.CH3

To about 42 grams of butyric anhydride, chilled in an ice bath, is addedwith stirring, 0.3 grams of concentrated sulfuric acid, and this mixtureis added, portionwise over a period of about 10 minutes, to 41 grams(0.25 mole) of 4-phenyl-1,3-dioxane. The mild exothermic reaction thatensues is controlled by external cooling, if necessary, so that thetemperature of the reaction mixture does not rise above and, preferablyis maintained within the range of about 30 C. to 40 C. The reactionmixture is allowed to stand overnight, then about 1 gram of sodiumacetate is added to inactivate sulfuric acid present, the mixture isfiltered to remove separated sodium sulfate and then the3-pheny1-2-oxa-1,5-pcntanediol dibutyrate is pyrolyzed as follows:

The diester is introduced slowly over a period of about 35 minutes, intoa stillpot containing about 1.5 grams of fused potassium bisulfate,heated by an oil bath heated at 240 C. to 245 C. The stillpot pressureis maintained at about 17 to 18 millimeters of mercury. The heating ofthe pot is so controlled that the distillate temperature is about C.after seven minutes operation and gradually rises to a maximum withinthe range of 155 C. to C. The distillate is collected, dissolved inbenzene, washed with water and dilute sodium bicarbonate solution,shaken with dilute sulfuric acid, washed again with water until thewashings are neutral, and dried. The solvent is removed by distillationand the still residue is fractionally distilled at a vacuum of 1millimeter of mercury. The fraction boiling at 124 C. to 126 C. iscollected and is found to be cinnamyl butyrate, obtained in a yield ofabout 52% of the calculated (saponification equivalent, calculated,204.1, found, 202.2).

It will be apparent to those versed in the art to which this inventionrelates that minor modifications may be made in the processes describedwithout departing from the scope of the invention.

Having thus described the subject matter of the invention, what it isdesired to secure by Letters Patent is:

1. The process for producing organic carboxylic acid esters ofsubstituted allyl alcohols that comprises subjecting to pyrolysis, at atemperature within the range of about 150 C. to about 300 C. and at areduced pressure of at most about 50 millimeters of mercury, a compoundrepresented by the formula wherein R1 is phenyl and R2 and R3 areradicals selected from the group consisting of alkyl groups comprisingat most 3 carbon atoms and phenyl, and recovering from the pyrolysismixture an ester of the formula wherein R1 is phenyl and R2 and Rs areradicals selected from the group consisting of alkyl groups comprisingat most 3 carbon atoms and phenyl, and recovering from the pyrolysismixture an ester of the formula wherein R1 and R2 have the significanceaforesaid.

3. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is potassium bisulfate.

4. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is p-toluenesulfonic acid.

5. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is potassium bisulfate and R2 and Rs are methyl.

6. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is p-toluenesulfonic acid and R2 and R3 are methyl.

7. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is potassium bisulfate and R2 and R3 are ethyl.

8. The process defined in claim 2 wherein the relatively non-volatileacidic catalyst is potassium bisulfate and R2 and Rs are n-propyl.

9. The process defined in claim 1 wherein R2 and R3 are methyl.

Boris: C. A. 22, 3626 (1928). Arundale et al.: Chem. Reviews, vol. 51,pp. 506-507, 535.

1. THE PROCESS FOR PRODUCING ORGANIC CARBOXYLIC ACID ESTERS OFSUBSTITUTED ALLYL ALCOHOLS THAT COMPRISES SUBJECTING TO PYROLYSIS, AT ATEMPERATURE WITHIN THE RANGE OF ABOUT 150*C. TO ABOUT 300*C. AND AT AREDUCED PRESSURE OF AT MOST ABOUT 50 MILLIMETERS OF MERCURY, A COMPOUNDREPRESENTED BY THE FORMULA